This proposal is to study the effects of local hyperthermia alone, ionizing radiation alone, and these two treatment modalities combined on the development of lymphatic and hematogenous metastases. These studies will be conducted in C57BL/6 mice bearing syngeneic poorly immunogenic melanomas in their feet, the precise metastatic potential of which is related to primary tumor size. Treatment will be done at two primary tumor sizes, either microscopic (mic) or macroscopic (mac) in order to address the possible contribution of tumor blood supply to the mechanisms of metastasis in this model. The primary tumor and regional lymph nodes will be surgically removed at intervals after treatment and metastases examined histologically. Mice will be sacrificed at precisely defined times in order to quantitate the incidence and numbers of metastases in lungs, ovaries and other systemic sites. The final experiments proposed will be to examine the effects of these modalities on overall survival. The results of these studies will provide evidence for the role of hyperthermia and ionizing radiation on the development of metastases from primary tumors following treatment.